J Hepatol. 2010 Dec 8. [Epub ahead of print]
Féray C.
INSERM U948, Hôtel-Dieu, 9 quai Moncousu, Nantes, France.
Abstract
COMMENTARY ON: Viral entry and escape from antibody-mediated neutralization influence hepatitis C virus reinfection in liver transplantation. Samira Fafi-Kremer, Isabel Fofana, Eric Soulier, Patric Carolla, Philip Meuleman, Geert Leroux-Roels, Arvind H. Patel, François-Loïc Cosset, Patrick Pessaux, Michel Doffoël, Philippe Wolf, Françoise Stoll-Keller and Thomas F. Baumert.©The Rockefeller University Press. The Journal of Experimental Medicine, 2010; 207: 2019-2031. Abstract reprinted with permission from the Rockefeller University Press. End-stage liver disease caused by chronic hepatitis C virus (HCV) infection is a leading cause for liver transplantation (LT). Due to viral evasion from host immune responses and the absence of preventive anti-viral strategies, reinfection of the graft is universal. The mechanisms by which the virus evades host immunity to re-infect the liver graft are unknown. In a longitudinal analysis of six HCV-infected patients undergoing LT, we demonstrate that HCV variants re-infecting the liver graft were characterized by efficient entry and poor neutralization by antibodies present in pre-transplant serum compared with variants not detected after transplantation. Monoclonal antibodies directed against HCV envelope glycoproteins or a cellular entry factor efficiently cross-neutralized infection of human hepatocytes by patient-derived viral isolates that were resistant to autologous host-neutralizing responses. These findings provide significant insights into the molecular mechanisms of viral evasion during HCV reinfection and suggest that viral entry is a viable target for prevention of HCV reinfection of the liver graft.
Copyright © 2010. Published by Elsevier B.V.
PMID: 21167852 [PubMed - as supplied by publisher]
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